Here are some thoughts and reflections, from Joel Sandler at Cello Health who has just stepped off the stage at BioTrinity 2019, after chairing a panel entitled “What’s New in Neurodegenerative Disease?”. Here are some high-level takeaways from the panel and the state of the field in general.

My panelists included Jenny Laird (VP, Search & Evaluation, Lilly),  Jenny Barnett (CSO, Cambridge Cognition), Ruth McKernan CBE (Senior Consultant, Dementia Discovery Fund), and Simon Stott (Deputy Director of Research, The Cure Parkinson’s Trust), each of whom was able to provide a unique perspective on lessons learned, challenges, and opportunities in the development of novel therapeutics to address this assemblage of diseases, each of which are characterised by tremendous unmet need, commercial opportunity, and clinical risk.

With the recent failure of Biogen/Eisai’s anti-amyloid antibody candidate aducanumab, there seemed to be both scepticism and excitement around next-wave approaches. Panellists agreed that, despite the toll taken by high-cost clinical failures to date, unmet need and hence funding will not dry up any time soon. That said, there is an earnest desire for clinical wins suitably sized to catalyze the field and incentivise investors (traditional dilutive capital, Pharma partners, government funds, charitable organizations, etc.) needed to drive a much higher level innovation.

To this end, much was said about the importance of biomarkers (both biopsy-derived and non-invasive diagnostics such as imaging and serum-derived signatures) as a means to enable early detection, patient stratification, and monitoring of therapeutic performance. That said, the ability to diagnose patients in the earlier (e.g. prodromal) stages of disease provides minimal value in the absence of actionable interventions, the development of which will be both costly and time-consuming. On the other hand, the ability of diagnostics to better define smaller, more homogeneous subpopulations within broader disorders like Alzheimer’s and Parkinson’s was repeatedly mentioned as a means to de-risk therapeutic opportunities in advance of committing huge sums needed to support large Phase 3 studies, all of which have to date been doomed to failure. Validation of surrogate endpoints as means to connect the dots between therapeutic administration and cognitive or functional outcomes was also regarded as an essential ingredient for successful clinical development.

In terms of therapeutic candidates, panellists were somewhat ambivalent as to the clinical meaning of symptomatic therapies, or even whether and how symptomatic vs. disease-modifying approaches should be categorised. Additional approaches such as those targeting neuroinflammation or the microbiome could play important roles, though the biology surrounding these components of disease pathology is far from clear at this stage.

Ultimately, panellists seemed most excited by gene therapies positioned to address specific aberrant targets from monogenic patient subsets or molecules implicated to play more pleiotropic roles in disease aetiology. Gene therapies, including AAV- and ASO-based approaches in diseases like Huntington’s and Parkinson’s were universally lauded as compelling approaches, with the added benefit of potentially being positioned to address said homogenous subsets needed to furnish expedited paths to market in advance of expansion into broader disease populations (e.g. LRRK2-positive Parkinson’s).

Despite the clinical and commercial risk that has come to dominate characterization of these disorders, panellists and audience members alike seemed strikingly optimistic about the prospects for clinical innovation. The field has suffered numerous blows, and the hope of achieving clinical success via empirical approaches to clinical development appears to be on the wane. But need and funds remain, and those innovators endeavouring to understand the alignment of the scientific underpinnings behind the value proposition of their therapeutic candidates with the enormously-complex but nonetheless, quantifiable biology driving disease processes will ultimately rule the day.